The current epidemic of sexually transmitted diseases (STDs) is characterized by a growing list of organisms (bacterial, viral, fungal and protozoan) responsible for a large number of serious diseases, disproportionately affecting adolescent and minority populations. The problem is exacerbated by the emergence of antibiotic and drug resistant organisms, and is currently one of the major public health crises in the United States. The existing approaches to the control of this epidemic are prevention, detection and treatment. Currently, prevention means education, easy access to barrier methods (primarily condoms), and to a lesser extent, the use of microbicides. Unfortunately, the only widely used microbicide is nonoxynol-9 and both its efficacy and safety have recently been questioned. The purpose of this project is to develop new topical microbicides suitable for the prevention of a wide variety of sexually transmitted diseases (STDs) including AIDS. The research is focused on a patented technology involving amphoric surface active molecules, known as C31G. The C31G technology employs a mixture of two synthetic molecules, an alkyl amine oxide and an alkyl betaine, that form a mixed micelle demonstrating a broad spectrum antibacterial and antiviral activity. The present proposal is designed to carry out structure-function studies with a series of alkyl amine oxides and alkyl betaines in an attempt to selectively enhance microbicidal activity and decrease toxicity for mammalian cells. Once the ideal C31G formulae is obtained, additional studies will be carried out to formulate the microbicide into a form that has wide acceptability. This will involve the addition of excipients and the design of a new delivery system which will allow for safe and discrete application of vaginal microbicides in a form that is under female control, and can be used without male knowledge. This proposal is part of a larger program project whereby new- microbicides will be evaluated against a large panel of STD organisms including bacteria (Treponema, Chlamydia, Neisseria), yeast (Candida), and viruses (HIV, HSV, HPV). To demonstrate low mammalian cell toxicity both in vitro (cell culture) and animal models will be employed.